Pseudomonas aeruginosa is an opportunistic pathogen that causes a variety of acute infections especially in cystic fibrosis patients, mechanically ventilated patients, burn victims and immunocompromised individuals. P. aeruginosa infections are recognized by the medical community as particularly worrisome and difficult to treat, especially multi-drug resistant (MDR) strains in the hospital setting. A patient's prognosis for recovery from an infection caused by P. aeruginosa is enhanced when the diagnosis is made and appropriate treatment initiated as early in the course of the infection as possible, before the number of bacteria in the host becomes overwhelming and much more difficult to bring under control.
Patients suffering from major burns are especially vulnerable as they have extensive disruption of the skin barrier, with a concurrent suppression of the immune system. These conditions expose the burn area to bacterial wound colonization that can lead to burn wound infection, sepsis, multi-organ failure and subsequent death. Bacterial infection is the leading cause of death in major burns (responsible to 50-80% of overall thermal injury mortality), and P. aeruginosa is the most prevalent pathogen isolated from burn wound infections mainly due to its high persistence in the environment and its high intrinsic antibiotic resistance. Moreover, excessive antibiotic pressure in burn units has resulted in the emergence of multidrug-resistant strains of P. aeruginosa (Edward-Jones et al., 2003, Singh et al., 2003), the emergence of which underscores the clinical need to develop new classes of antibacterial therapeutics that can target centrally important proteins implicated in P. aeruginosa virulence.
P. aeruginosa is the scourge of hospital-associated pneumonias (HAP) of which ventilator-associated pneumonia (VAP) is routinely observed in Intensive Care Units. P. aeruginosa also causes infections in immune suppressed individuals (eg. cancer patients, patients awaiting transplantation, AIDS patients, premature babies). Also, P. aeruginosa causes infections at surgical sites, is responsible for urinary tract infections and of course is a relentless pulmonary infection in Cystic Fibrosis patients. Additionally, patients suffering from chronic obstructive pulmonary dysfunction (COPD) and bronchiectasis are highly susceptible to P. aeruginosa infections. Healthy individuals may also be susceptible to P. aeruginosa; for example, contact lens users are prone to P. aeruginosa infections and Swimmer's ear (also called otitis externa) is often caused by P. aeruginosa. 
Immunotherapeutic strategies focusing on immunization (active or passive) and treatment targeting P. aeruginosa virulence-associated factors, such as elastase, protease, and exotoxin A, have been described in the literature and have showed limited success in the prevention and treatment of P. aeruginosa infections in animal models (Drake et al., 1987; Landsperger et al., 1994; Matsumoto et al., 1999; Steiner et al., 1998; Eaves-Pyles et al., 1999). Moreover, anti-lipopolysaccharide antibodies were found to be ineffective against a broad spectrum of P. aeruginosa isolates because of the presence of various lipopolysaccharide serotypes.
Flagellin protein, the principal component of bacterial flagella, has long been recognized as an important virulence factor in P. aeruginosa infections. Two major antigenic groups of flagella have been identified; type A, also known as HE comprising five sub-types designated a0-4, and type B, also known as H2, having no sub-groups (Lanyi et al, 1970; Ansorg, 1978). The ‘propeller-like’ rotation as a result of flagellin polymerization is crucial for bacterial locomotion and survival and it is a contributing factor to bacterial invasion. Indeed, sub-type monoclonal antibodies (mAbs) raised against endogenous P. aeruginosa flagellins have been shown to afford protection in different animal models of P. aeruginosa infection (Drake et al., 1987; Rosok et al., 1990; Oishi et al., 1993; Landsperger et al., 1994; Matsumoto et al., 1999). U.S. Pat. No. 4,834,976 discloses monoclonal antibodies or antigen binding fragment thereof capable of specifically reacting with P. aeruginosa bacteria flagella type A or type B, but not both, which are said to be protective in vivo against said bacteria.
The flagellum, which mediates rapid bacterial movement, has an important role in bacterial dissemination and ultimately the progression of local bacterial colonization into an overwhelming invasive disease. Studies using various gram-negative flagellated bacteria, as well as flagellin deletion strains have demonstrated that flagellin is a ‘double-edged sword’. Besides its role in bacterial motility and cellular invasion, isolated flagellin protein or intact P. aeruginosa harboring the flagellum appendage, can trigger inflammatory cells to produce an array of different pro-inflammatory molecules, including those involved in innate immunity. Flagellin's mode of action is mediated through high affinity binding towards the Toll-5 receptor (TLR5) whose activation results in the nuclear translocation of NF-κB and Elk-1 with enhanced transcription of immune response genes. Recent molecular studies revealed that the proinflammatory induction by flagellin is located at both the N′ and C′-terminal regions of the molecule, rendering flagella, a highly feasible, “appendage-like” target for immunotherapy. The noxious effects of flagellin clearly highlights flagellin's role in experimental systemic tissue injury and circulatory shock.
Recently, it has been shown that a large percentage of P. aeruginosa strains from CF patients are non-motile, yet do possess an intact flagellum (and associated flagellin proteins) which has been essentially rendered disabled in terms of motility. Nevertheless, these non-motile strains are still damaging since their disabled flagellin retains its biological activity at lung TLR5 causing profound local inflammation. Thus, antibodies targeting P. aeruginosa flagellin should be protective against both motile and non-motile (flagellin positive) strains. Because most clinical P. aeruginosa isolates are flagellated, and given that there are only two major antigenic types, antiflagellum immunotherapy has been proposed as a possible treatment for P. aeruginosa infections.